Phlegmasia alba dolens (also colloquially known as milk leg or white leg) is part of a spectrum of diseases related to deep vein thrombosis. Historically, it was commonly seen during pregnancy and in mothers who have just given birth. In cases of pregnancy, it is most often seen during the third trimester, resulting from a compression of the left common iliac vein against the pelvic rim by the enlarged uterus. Today, this disease is most commonly (40% of the time) related to some form of underlying malignancy. Hypercoagulability (a propensity to clot formation) is a well-known state that occurs in many cancer states. The incidence of this disease is not well reported.

The disease presumably begins with a deep vein thrombosis that progresses to total occlusion of the deep venous system. It is at this stage that it is called phlegmasia alba dolens. It is a sudden (acute) process. The leg, then, must rely on the superficial venous system for drainage. The superficial system is not adequate to handle the large volume of blood being delivered to the leg via the arterial system. The result is edema, pain and a white appearance ("alba") of the leg.

The next step in the disease progression is occlusion of the superficial venous system, thereby preventing all venous outflow from the extremity. At this stage it is called phlegmasia cerulea dolens. The leg becomes more swollen and increasingly more painful. Additionally, the edema and loss of venous outflow impedes the arterial inflow. Ischemia with progression to gangrene are potential consequences. Phlegmasia alba dolens is distinguished, clinically, from phlegmasia cerulea dolens in that there is no ischemia.

Phlegmasia cerulea dolens (literally: "painful blue edema") is an uncommon severe form of deep venous thrombosis which results from extensive thrombotic occlusion (blockage by a thrombus) of the major and the collateral veins of an extremity. It is characterized by sudden severe pain, swelling, cyanosis and edema of the affected limb. There is a high risk of massive pulmonary embolism, even under anticoagulation. Foot gangrene may also occur. An underlying malignancy is found in 50% of cases. Usually, it occurs in those afflicted by a life-threatening illness.

This phenomenon was discovered by Jonathan Towne, a vascular surgeon in Milwaukee, who was also the first to report the "white clot syndrome" (now called heparin induced thrombocytopenia [HIT]). Two of their HIT patients developed phlegmasia cerulea dolens that went on to become gangrenous.

Treatment by Catheter directed thrombolytic therapy.

The risk of VTE is increased in pregnancy by about five times because of a more hypercoagulable state, a likely adaptation against fatal postpartum hemorrhage. Additionally, pregnant women with genetic risk factors are subject to a roughly three to 30 times increased risk for VTE. Preventative treatments for pregnancy-related VTE in hypercoagulable women were suggested by the ACCP. Homozygous carriers of factor V Leiden or prothrombin G20210A with a family history of VTE were suggested for antepartum LMWH and either LMWH or a vitamin K antagonist (VKA) for the six weeks following childbirth. Those with another thrombophilia and a family history but no previous VTE were suggested for watchful waiting during pregnancy and LMWH or—for those without protein C or S deficiency—a VKA. Homozygous carriers of factor V Leiden or prothrombin G20210A with no personal or family history of VTE were suggested for watchful waiting during pregnancy and LMWH or a VKA for six weeks after childbirth. Those with another thrombophilia but no family or personal history of VTE were suggested for watchful waiting only. Warfarin, a common VKA, can cause harm to the fetus and is not used for VTE prevention during pregnancy.

Some malignancies, especially gliomas (25%), as well as adenocarcinomas of the pancreas and lung, are associated with hypercoagulability (the tendency to form blood clots) for reasons that are incompletely understood, but may be related to factors secreted by the tumors, in particular a circulating pool of cell-derived tissue factor-containing microvesicles. Some adenocarcinomas secrete mucin that can interact with selectin found on platelets, thereby causing small clots to form.

In patients with malignancy-associated hypercoagulable states, the blood may spontaneously form clots in the portal vessels, the deep veins of the extremities (such as the leg), or the superficial veins anywhere on the body. These clots present as visibly swollen blood vessels (thrombophlebitis), especially the veins, or as intermittent pain in the affected areas.

The three factors of Virchow's triad—venous stasis, hypercoagulability, and changes in the endothelial blood vessel lining (such as physical damage or endothelial activation)—contribute to DVT and are used to explain its formation. Other related causes include activation of immune system components, the state of microparticles in the blood, the concentration of oxygen, and possible platelet activation. Various risk factors contribute to DVT, though many at high risk never develop it.

Acquired risk factors include the strong risk factor of older age, which alters blood composition to favor clotting. Other important acquired risk factors include major surgery and trauma, both of which may increase the risk because of tissue factor from outside the vascular system entering the blood. In orthopedic surgery, venous stasis may be temporarily provoked by a cessation of blood flow as part of the procedure. Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor. Pregnancy causes blood to favor clotting, and in the postpartum, placental tearing releases substances that favor clotting. Oral contraceptives and hormonal replacement therapy increase the risk through a variety of mechanisms, including altered blood coagulation protein levels and reduced fibrinolysis.

The disease term venous thromboembolism (VTE) includes the development of either DVT or pulmonary embolism (PE). Genetic factors that increase the risk of VTE include deficiencies of three proteins that normally prevent blood from clotting—protein C, protein S, and antithrombin—in addition to non-O blood type and mutations in the factor V and prothrombin genes. Deficiencies in antithrombin, protein C, and protein S are rare but strong, or moderately strong, risk factors. These three thrombophilia increase the risk of VTE by about 10 times. Factor V Leiden, which makes factor V resistant to inactivation by activated protein C, and the genetic variant prothrombin G20210A, which causes increased prothrombin levels, are predominantly expressed in Caucasians. They moderately increase risk for VTE, by three to eight times for factor V Leiden and two to three times for prothrombin G20210A. Having a non-O blood type roughly doubles VTE risk. Non-O blood type is common in all races, making it an important risk factor. Individuals without O blood type have higher blood levels of von Willebrand factor and factor VIII than those with O blood type, increasing the likelihood of clotting.

Some risk factors influence the location of DVT within the body. In isolated distal DVT, the profile of risk factors appears distinct from proximal DVT. Transient factors, such as surgery and immobilization, appear to dominate, whereas thrombophilias and age do not seem to increase risk. In upper-extremity DVT, the most important risk factor is having a central venous catheter, and thoracic outlet syndrome also increases risk.

The Trousseau sign of malignancy or Trousseau's syndrome is a medical sign involving episodes of vessel inflammation due to blood clot (thrombophlebitis) which are recurrent or appearing in different locations over time (thrombophlebitis migrans or migratory thrombophlebitis). The location of the clot is tender and the clot can be felt as a nodule under the skin. Trousseau's syndrome is a rare variant of venous thromboembolism (VTE) that is characterized by recurrent, migratory thrombosis in superficial veins and in uncommon sites, such as the chest wall and arms. This syndrome is particularly associated with pancreatic, gastric and lung cancer and Trousseau's syndrome can be an early sign of cancer

, sometimes appearing months to years before the tumor would be otherwise detected. Heparin therapy is recommended to prevent future clots. The Trousseau sign of malignancy should not be confused with the Trousseau sign of latent tetany caused by hypocalcemia.

Melancholia (from , '), also lugubriousness, from the Latin "lugere", to mourn; moroseness, from the Latin "morosus", self-willed, fastidious habit; wistfulness, from old English "wist": intent, or saturnine, was a concept in ancient and pre-modern medicine. Melancholy was one of the four temperaments matching the four humours. In the 19th century, "melancholia" could be physical as well as mental, and melancholic conditions were classified as such by their common cause rather than by their properties.

The name "melancholia" comes from the old medical belief of the four humours: disease or ailment being caused by an imbalance in one or other of the four basic bodily liquids, or humours. Personality types were similarly determined by the dominant humor in a particular person. According to Hippocrates and subsequent tradition, melancholia was caused by an excess of black bile, hence the name, which means "black bile", from Ancient Greek μέλας ("melas"), "dark, black", and χολή ("kholé"), "bile"; a person whose constitution tended to have a preponderance of black bile had a "melancholic" disposition. In the complex elaboration of humorist theory, it was associated with the earth from the Four Elements, the season of autumn, the spleen as the originating organ and cold and dry as related qualities. In astrology it showed the influence of Saturn, hence the related adjective "saturnine".

Melancholia was described as a distinct disease with particular mental and physical symptoms in the 5th and 4th centuries BC. Hippocrates, in his "Aphorisms", characterized all "fears and despondencies, if they last a long time" as being symptomatic of melancholia. When a patient could not be cured of the disease it was thought that the melancholia was a result of demonic possession.

In his study of French and Burgundian courtly culture, Johan Huizinga noted that "at the close of the Middle Ages, a sombre melancholy weighs on people's souls." In chronicles, poems, sermons, even in legal documents, an immense sadness, a note of despair and a fashionable sense of suffering and deliquescence at the approaching end of times, suffuses court poets and chroniclers alike: Huizinga quotes instances in the ballads of Eustache Deschamps, "monotonous and gloomy variations of the same dismal theme", and in Georges Chastellain's prologue to his Burgundian chronicle, and in the late fifteenth-century poetry of Jean Meschinot. Ideas of reflection and the workings of imagination are blended in the term "merencolie", embodying for contemporaries "a tendency", observes Huizinga, "to identify all serious occupation of the mind with sadness".

Painters were considered by Vasari and other writers to be especially prone to melancholy by the nature of their work, sometimes with good effects for their art in increased sensitivity and use of fantasy. Among those of his contemporaries so characterised by Vasari were Pontormo and Parmigianino, but he does not use the term of Michelangelo, who used it, perhaps not very seriously, of himself. A famous allegorical engraving by Albrecht Dürer is entitled "Melencolia I". This engraving has been interpreted as portraying melancholia as the state of waiting for inspiration to strike, and not necessarily as a depressive affliction. Amongst other allegorical symbols, the picture includes a magic square and a truncated rhombohedron. The image in turn inspired a passage in "The City of Dreadful Night" by James Thomson (B.V.), and, a few years later, a sonnet by Edward Dowden.

The most extended treatment of melancholia comes from Robert Burton, whose "The Anatomy of Melancholy" (1621) treats the subject from both a literary and a medical perspective. Burton wrote in the 17th century that music and dance were critical in treating mental illness, especially melancholia.

in 10th century Persian physician Al-Akhawayni describes Melancholia as a chronic illness and relates it to brain, which is one of the main aspects of his view on Melancholia. He describes Melancholia’s initial clinical manifestations as "suffering from an unexplained fear, inability to answer questions or providing false answers, self-laughing and self-crying and speaking meaninglessly, yet with no fever"

In the Encyclopédie of Diderot and d'Alembert, the causes of melancholia are stated to be similar to those that cause Mania: "grief, pains of the spirit, passions, as well as all the love and sexual appetites that go unsatisfied."